Protein kinase C, PKC, is a family of widely distributed signal transduction proteins important for cell growth, differentiation, and other responses. PKC is activated by growth factors, hormones, and other external messengers via stimulation of phospholipase C and the generation of the second messengers, inositol triphosphate and diacylglycerol. All members of the PKC family share significant sequence homology and perform signal transduction via protein phosphorylation. Almost all cell types express one or more isoforms of PKC.
The activity of an endogenous inhibitor of PKC has been detected in bovine, avian, murine, and human tissues. The first complete primary structure of an endogenous inhibitor of protein kinase C, PKCI-1, was derived from bovine brain (Pearson, J D et al (1990) J Biol Chem 265: 4583-4591). PKCI-1 has a specific site of interaction with PKC and inhibits the phosphorylation ability of PKC. In addition to the bovine sequence, a complete amino acid sequence of PKCI-1 has been deduced from the maize, rat, and human genes (Simpson G G et al (1994) Blochim Biophys Acta 1222: 306-308; Waller S J and Murphy D (1994), unpublished; Brzoska P M et al (1995) PNAS USA 92: 7824-7828). The bovine PKCI-1 was shown to be a zinc (Zn) binding protein (Simpson et al, supra). The site of Zn binding has been localized to a 11 amino acid fragment (Mozier et al (1991) FEBS Lett 279:14-18), and the Zn binding domain is conserved among PKCI-1 molecules of other species.